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Issue 19, 2018
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Discovery of novel inhibitors of RNA silencing suppressor P19 based on virtual screening

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Abstract

To control plant viruses, viral RNA silencing suppressors are important drug targets due to their key roles in interfering antiviral RNA silencing. Here we have presented a strategy, combining virtual and experimental screening, to discover the inhibitors of viral suppressor. By docking 157 026 compounds from a natural product library into P19 model, eighteen candidate compounds were selected. Candidates VS2, VS12, VS14 and VS15 displayed strong binding ability to P19 in the surface plasmon resonance imaging assay with KD values of 136.2, 111.6, 81.2 and 124.5 nM, respectively. Then the inhibition activities of these inhibitors on the association between P19 and siRNA were also affirmed by electrophoretic mobility shift assay. Moreover, the antiviral effects on plants showed that compounds VS14 and VS15 both exhibited antiviral activities against Tomato bushy stunt virus (TBSV) in vivo with inhibition rates of 32.35% and 16.61% in 11 dpi, respectively. This strategy would be a powerful tool for the discovery of novel antiviral agents and provide new insights into the control of plant viruses.

Graphical abstract: Discovery of novel inhibitors of RNA silencing suppressor P19 based on virtual screening

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Supplementary files

Article information


Submitted
10 Feb 2018
Accepted
06 Mar 2018
First published
16 Mar 2018

This article is Open Access

RSC Adv., 2018,8, 10532-10540
Article type
Paper

Discovery of novel inhibitors of RNA silencing suppressor P19 based on virtual screening

F. Hu, R. Lei, Y. Deng, J. Wang, G. Li, C. Wang, Z. Li and S. Zhu, RSC Adv., 2018, 8, 10532
DOI: 10.1039/C8RA01311J

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